Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity

Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity.

Kévin Cottet , Bin Xu (1) , Pascale Coric (2) , Serge Bouaziz (3) , Michel Michel (4) , Michel Vidal (5) , Marie-Christine Lallemand (6) , Sylvain Broussy (7) , Sylvie Michel (8)

1 Yangtze Delta Region Institute of Tsinghua University [Zhejiang]
2 LCRB - UMR 8015 - Laboratoire de cristallographie et RMN biologiques
3 UPCG - UMR_S 640/UMR 8151 - Unité de Pharmacologie Chimique et Génétique
4 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
5 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
6 UMR 8638 - Equipe Pharmacognosie
7 LCC - Laboratoire de chimie de coordination
8 LMT - Laboratoire de Mécanique et Technologie

Natural products guttiferone A, hyperforin, and aristoforin were able to inhibit or increase SIRT1 catalytic activity, depending on protein concentration and presence of detergent. On the basis of NMR data for guttiferone A, we demonstrated that the aggregation state of the natural product played a crucial role for its interaction with the enzyme. These results are useful to interpret future in vitro structure-activity relationship studies on these natural products in the quest of their biological target(s).

Domaines: Biologie structurale [q-bio.BM]

Kévin Cottet, Bin Xu, Pascale Coric, Serge Bouaziz, Michel Michel, et al.. Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity. Journal of Medicinal Chemistry, 2016, 59 (20), pp.9560-9566. ⟨10.1021/acs.jmedchem.6b01182⟩. ⟨hal-02122343⟩